Antivitamin



Patented May '9, 1944 UNITED STATES PATENT OFFICE ANTIVI'I'AMIN EsmondE. Snell, Austin, Tex, neither to Re search Corporation, New York, N.Y., a corporation of New York v No Drawing. Application til 23, 1943,Serial No. 484,2 13 Claims. (Cl. 2 60-513) resultswhen preparing thecorresponding barium compound, The free sulfonic acid compoundconveniently may be prepared by first preparing This invention relatesto the provision of compounds which are antagonistic to the growthpromoting or supporting properties of pantothenic acid.

I have found that whereas pantothenic acid is 1 necessary to the growthof certain organisms, m such as Lactobacillus arabinosus, certain]'c'ompounds which differ from pantothenic acid ina.

ta t ta in which X stands for a member of the group consisting ofhydrogen and the alkali and alka-. line earth metals. As will beapparent, such compounds differ from pantothenic acid inthat the COOHgroup of the latter is replaced in the former by the sulfo group, SOaX.

The compounds are prepared, in accordance with my invention, by theinteraction of a-hydroxy-p,p-dimethyl-y-butyrolactone with taurine(B-aminoethyl sulfonic acid) and its alkali and alkaline earth metalsalts.

Example 1 5 grams of levo-a-hydroxy-p,p-dimethylybutyrolactone wasmelted at 100 C. To the mdt was added 5.7 grams'of dry powdered sodiumsalt of taurine. The mixture was maintained at 120-130 C. for 3 hourswith occasional stirring.

The melt became clear and homogeneous and solidified on cooling.

The reaction involved proceeds according to' the equation 7 on O CHr-

Hg-CHzBOtNii H HIOH A higher fusion temperature may be employed tohasten the reaction and is necessary for best he bariumysalt and thenremoving the barium with sulfuric acid.

The product of the foregoing example was te sted 'for growth inhibitingpowers by use of ';Lactobacillus arabinosus in the medium described by'Shell and Mitchell in Proceedings of the National Academy of Science,vol. :27, page 1 (1941) to which was added each of uracil, adenine andguanine. The medium contained only 0.3 of calcium pantothenate per 10cc. Addition of 300 of the above product or condensate completelyinhibited growth. The growth inhibition produced by the addition'of10,000 of the product to 10 cc. of the medium was, however, completelyreversed by a simultaneous addition of 30 of calcium pantothenate.

The product made according to the foregoing specific example containsabout 80% of the condensation product as indicated by the extent of thereaction which was measured by determining the decrease in free aminonitrogen from the beginning to the end of the reaction. It has beenfound, however, that the products made by the condensation of differentproportions of the lactone and the taurine salt, by carrying out thecondensation at slightly different temperatures. by carrying out thecondensation with longer and shorter periods of heating and by thesubstitution of taurine or the barium salt thereof for the sodium saltof taurine all exhibited the same growth inhibiting effect. On the otherhand, neither taurine alone nor the lactone(z-hydroxy-ap-dimethyl-y-butyrolactone) alone in quantities equivalentto those of the condensation product used in the above described testproduced any detectable growth inhibition. It follows, therefore, thatit is the condensation product of the taurine and the lactone in theform of either the free acid or a salt thereof which exhibits the growthinhibiting effect an 9 tagonistic to the growth promoting effect ofpantothenic acid. Various metal salts other than the sodium salt may beemployed, such as the lithium, potassium, calcium, strontium and bariumsalts.

Eitample 2 To 7.8 grams of dl-a-hydroxy-p,p-dimethyl-'ybutyrolactonewere added 11.2 grams of the dry powdered barium salt of taurine. Themixture was heated at 145-150 for 1 hour, then held at -140" for 2hours. The viscous, yellowish mass set to a brittle solid. On testingwith Lactobacillus arabinosus the product had the same growthinhibitingproperties possessed by the sodium salt. Quantitative comparison of thegrowth inhibiting properties of this melt with those of the sodium saltindicated an approximately quantitative yield (CSHNOSNS) 2Ba{calculatednN 4.34, Ba 21.27

Example 3 The free acid is most conveniently prepared from the bariumsalt by double decomposition according to the equation: I

(CaHlsOsNS) zBa-i-H2SOr BaSO4+2CaH11OsNS To 4' grams ofbarium saltprepared as described in Example 2 and dissolved in 30 cc. of water thetheoretical amount (0.61 gm.) of H2SO4 was added. The solution waswarmed briefly at 50, and the insoluble barium sulfate filtered out. Thesolution when concentrated to dryness yielded a residue consisting ofthe free acid The product was tested for growth-inhibiting propertieswithLactobacillus arabinosus as pre- A viously described, and showedfull activity.

Found.. N 4;.2'7, Ba 21.29

analysis by-the following procedure.

.to the having physiological activity which is antagonistic rowthpromoting properties of pantothenic acid which comprises heating ana-hy- 'droxy-pp-dimethyl- -butyrolactone with a taurine compound of theformula Nmcmcmsmx in which X stands for a member 01 the groupconsistingof hydrogen and the alkali and alkaline.

' earth metals.

This application is a continuation -in-part of my applicationserial No.400,152, filed June 27,

2. A process as defined in claim 1 in which X stands for hydrogen. I s

3. A process as defined in clallnl in which X stands for an alkalimetal.

4. A process as defined stands for an alkaline earth metal. I

5. A process as defined in claim 1 in which X stands for sodium.

6. A process as defined in claim 1 in which X stands for barium.

'7. A compound of .the formula CH1. 0 a g H l -c- -N-c-o-s0.x (5H JHa(EH in which X stands for a member of the group consisting of hydrogenand the alkali and alkaline earth metals. 8. A compound as defined inclaim 7 in which X stands for hydrogen.

9. A compounds as defined in claim '1 in which 'x stands for an alkalimetal.

10. A compound as defined in claim? in which X stands for an alkalineearth metal.

11. A compound as defined in claim X stands for sodium.

12. A compound as defined in claim 7 in which X stands for barium.

13. Process which comprises fusing a mixture of approximately 5 parts byweight of levo-m-hydroxy-;3,p-dimethylw-butyroiactone and approxi- 7 inwhich mately 5.7 parts by weight of the sodium salt of taurine.

ESMOND E. SNELL.

in claim 1 m which 2:

